Melanoma Tumor 'Dissolves' After 1 Dose of New Drug Combo

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A large melanoma tumor on a woman's chest disappeared so quickly
that it left a gaping hole in its place after she received a new
treatment containing two melanoma drugs, a new case report finds.

Doctors are still monitoring the 49-year-old woman, but she was
free of melanoma — a type of skin cancer that can be deadly — at
her last checkup, said the report's lead author, Dr. Paul
Chapman, an attending physician and head of the melanoma section
at the Memorial Sloan Kettering Cancer Center in New York.

The woman took the same two drugs as more than 100 people with
melanoma who took part in a recent study. For most of the
study participants who took these drugs, the combination worked
better than one drug alone. But the doctors were surprised
by how well the drug combination worked to treat this particular
woman's cancer — they had not anticipated that a melanoma tumor
could disappear so quickly that it would leave a cavity in the
body — and thus wrote the report describing her case.

"What was unusual was the magnitude [of recovery], and how
quickly it happened," Chapman told Live Science. However, doctors
are wary of the drug combination because it does not work for
everyone, and can have side effects, such as severe diarrhea.
[ 10
Do's and Don'ts to Reduce Your Risk of Cancer ]

Both the study of the drug combination and the woman's case
report were published Monday (April 20) in the New England
Journal of Medicine. The drug combination is part of a
relatively recent approach to treating melanoma with medications
that boost a person's own immune system, called immunotherapy.

One of the drugs in the combination was ipilimumab (sold under
the brand name Yervoy), which works by removing an inhibitory
mechanism that can stop certain immune cells from killing cancer
cells.

In the study, researchers combined ipilimumab with another drug,
called nivolumab (brand name Opdivo), which can prevent immune
cells called T cells from dying, Chapman said.

The U.S. Food and Drug Administration has approved ipilimumab and
nivolumab separately as melanoma drugs but has not approved their
combined use. The researchers' study was aimed at testing how the
two drugs worked when used in tandem.

In the study, doctors gave treatments to 142 people with
metastatic melanoma (melanoma that has spread to other parts of
the body) — some participants received the combination, and
others received ipilimumab plus a placebo. Neither the
participants nor their doctors knew who had received which
treatment until the trial had ended.

The new drug combination had better results than the
ipilimumab-plus-placebo treatment, the researchers found.

In one analysis, the researchers focused on 109 patients who did
not have a mutation in a gene called the BRAF gene. (BRAF
mutations are linked to a number of cancers, including melanoma,
and there are other melanoma drugs that target BRAF mutations.)
Among the 72 people in this group who took the combination, 61
percent saw their cancer
shrink, compared with just 11 percent of the 37 people in the
group who took only ipilimumab.

What's more, melanoma was undetectable in 22 percent of the
combination group at the end of the study, which was funded by
Bristol-Myers Squibb, which makes the drugs. None of the people
taking ipilimumab plus a placebo saw their melanoma disappear by
the time the study had ended.

Twenty-two percent may not sound high, but in the world of
melanoma treatment, it is significant, said Dr. Sylvia Lee, an
assistant professor of medicine at the University of Washington,
Seattle Cancer Care Alliance and Fred Hutchinson Cancer Research
Center. Lee was not involved in the new study, but she is working
with patients who are receiving the drug combination in Seattle.

A complete response to treatment is "the Holy Grail," she said.
"That's what everyone wants, where all of the cancer disappears.
We're talking about patients with stage IV melanoma. Usually, in
cancers, when someone has stage IV disease, for the majority of
people, it's no longer curable." [ Medicine's
Journey Through the Body: 4 Stages ]

It's unclear whether melanoma will reoccur in any of the patients
in the new study. Doctors are following them to see whether the
people who are taking the combination drugs live longer than
expected, Chapman said.

Side effects

However, the ipilimumab with nivolumab combination comes with
serious side effects, such as colitis (swelling of the colon),
diarrhea and problems with the endocrine glands (which produce
hormones).

About 54 percent of the patients in the study who were taking the
combination reported serious side effects, compared with 24
percent of the people taking only ipilimumab, the researchers
found.

The treatments are given three weeks apart, but some people can
tolerate only one or two treatments out of the suggested four
before they stop taking the medicine, Lee said. In the new study,
about 60 percent of the participants taking the combination
finished all four treatments, compared with 70 percent of the
ipilimumab-only group.

The side effects can be brutal, Lee said. "This is
diarrhea that is 25 to 40 times a day," she said.

Future trials may help researchers refine the number of
treatments needed and figure out how effective just one or two
treatments can be. The current trial is over, but certain cancer
centers are still offering the drug combination through an
expanded access program, which is how the woman whose tumor
disappeared got the medicine.

Her case shows that immunotherapy can work quickly: Her tumor
vanished within three weeks of receiving her first treatment, the
researchers found.

"I was astonished; I'd never seen anything like that," Chapman
said. "She said the tumor had just kind of dissolved."

However, the combination may pose a risk if it dissolves a tumor
somewhere else the body, and leaves a hole behind.

"I think that it is a huge concern," Lee said. "It is something
to consider if you do have a patient with a tumor [invading] a
vital organ."

The medications are also pricey. Ipilimumab costs $120,000 for
four treatments, and nivolumab is priced at $12,500 a month,
the Wall Street Journal reported.

Still, the drug combination may offer a new and promising
treatment for people with melanoma if the FDA approves it,
Chapman said.

"It kind of confirms an assumption that we've all had for many
decades: that the immune system can recognize cancers and can
kill large tumors if properly activated," Chapman said.